재발 및 불응성 급성림프모구백혈병에서의 표적치료제
Immuno-Target Therapy for Relapsed or Refractory Acute Lymphoblastic Leukemia
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Standard post-remission therapy for adult patients with high-risk acute lymphoblastic leukemia (ALL) is allogeneic hematopoietic cell transplantation (allo-HCT). However, 20–30% of patients treated with allo-HCT subsequently relapse, and their long-term survival outcomes are very poor even after the next allo-HCT. The poor survival outcomes reported by previous studies have mainly been due to low complete remission (CR) rates and high mortality from conventional salvage chemo-regimens, such as mitoxantrone plus etoposide plus cytarabine (MEC) or fludarabine plus cytarabine plus idarubicin (FLA-Ida). However, several novel agents with proven high remission rates and a good measurable residual disease response can now be administered. The representative novel agents recently introduced are blinatumomab (anti-CD19 bispecific T-cell engager) and inotuzumab ozogamicin (anti-CD22 antibody- calicheamicin conjugate). In South Korea, blinatumomab has been used since October 2016 and inotuzumab ozogamicin has been in use since October 2019 under coverage by the national insurance system. Studies on blinatumomab in Korea showed that this drug is effective when used as an early salvage line, even in patients who relapse after an initial allo-HCT. However, a previous study revealed that relapsed patients with a short CR duration of < 12 months post-HCT show a poor response to blinatumomab compared to patients with a longer CR duration. Also, some early relapsed cases with active acute graft-versus-host disease (GVHD) show aggravated GVHD with the use of blinatumomab. No real-world data are available in Korea for inotuzumab, but previous trials have reported a good CR and proceeding rates to allo-HCT comparable to blinatumomab. We have experienced hepatotoxicity including venoocclusive disease in post-HCT relapsed patients treated with inotuzumab.
Abstract
Standard post-remission therapy for adult patients with high-risk acute lymphoblastic leukemia (ALL) is allogeneic hematopoietic cell transplantation (allo-HCT). However, 20–30% of patients treated with allo-HCT subsequently relapse, and their long-term survival outcomes are very poor even after the next allo-HCT. The poor survival outcomes reported by previous studies have mainly been due to low complete remission (CR) rates and high mortality from conventional salvage chemo-regimens, such as mitoxantrone plus etoposide plus cytarabine (MEC) or fludarabine plus cytarabine plus idarubicin (FLA-Ida). However, several novel agents with proven high remission rates and a good measurable residual disease response can now be administered. The representative novel agents recently introduced are blinatumomab (anti-CD19 bispecific T-cell engager) and inotuzumab ozogamicin (anti-CD22 antibody- calicheamicin conjugate). In South Korea, blinatumomab has been used since October 2016 and inotuzumab ozogamicin has been in use since October 2019 under coverage by the national insurance system. Studies on blinatumomab in Korea showed that this drug is effective when used as an early salvage line, even in patients who relapse after an initial allo-HCT. However, a previous study revealed that relapsed patients with a short CR duration of < 12 months post-HCT show a poor response to blinatumomab compared to patients with a longer CR duration. Also, some early relapsed cases with active acute graft-versus-host disease (GVHD) show aggravated GVHD with the use of blinatumomab. No real-world data are available in Korea for inotuzumab, but previous trials have reported a good CR and proceeding rates to allo-HCT comparable to blinatumomab. We have experienced hepatotoxicity including venoocclusive disease in post-HCT relapsed patients treated with inotuzumab.
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